Reversal of Enantioselectivity in Aldol Reaction: New Data on Proline/γ-Alumina Organic–Inorganic Hybrid Catalysts

Abstract

We report new results on the aldol reactions between aldehydes of three different types (aromatic, aliphatic and cycloaliphatic) and acetone/cycloalkanones as reaction partners, driven by organic–inorganic hybrid catalyst Pro/γ-Al2O3. In contrast to the homogeneous liquid-phase reaction, over Pro/γ-Al2O3 reversal of the enantioselection in up to 20–40 % ee depending on the structure of the aldehyde was observed in reactions of acetone. Reversal of the ee in the presence of γ-Al2O3 cannot be generalized, as it has only been observed for acetone among the ketones studied by us. It was proven using methods of a great variety such as ultrasonic irradiation, reuse measurements on used catalyst and the filtrate of the first reaction, measurements on the l-Pro-l-Pro(OH) dipeptide, studies using mixtures of l-Pro and d-Pro that the organic–inorganic hybrid catalyst Pro/γ-Al2O3 formed in situ is responsible for reversal of the ee. In the reactions of cycloalkanones there is presumably competition between the liquid-phase and the surface reaction over Pro/γ-Al2O3 with preference for the former. Based on these results a surface reaction pathway was proposed. Although, the ees obtained under heterogeneous catalytic conditions are low, further studies may lead to application of this unusual phenomenon for obtaining chiral heterogeneous catalysts suitable for the preparation of the desired enantiomer of a chiral compound using the same chiral source.